PENTOXIFYLLINE INHIBITS T-CELL ADHERENCE TO KERATINOCYTES

In many inflammatory dermatoses leukocyte function-associated antigen- 1/intercellular adhesion molecule-1 mediated T-cell/keratinocyte adhes ion is considered to play an important role. Pentoxifylline (PTX), a m ethylxanthine derivative widely used for the symptomatic treatment of various vascular disorders, was recently found to have anti-inflammato ry effects. PTX can suppress tumor necrosis factor-alpha production an d function, and inhibits leukocyte-endothelial cell adherence. The aim of the present study was to investigate whether PTX also interferes w ith T-cell/keratinocyte binding. Peripheral blood T cells were activat ed with phorbol myristate acetate and co-incubated with interferon-gam ma- or tumor necrosis factor-alpha-stimulated keratinocytes (SVK 14 ce lls) in the presence or absence of PTX. Using an enzyme-linked immune cell adhesion assay PTX was found to inhibit T-cell/keratinocyte adhes ion in a dose-dependent manner. A similar inhibition was found when PT X was replaced by isobutylmethylxanthine, another methylxanthine deriv ative, or by a combination of two cyclic adenosine monophosphate analo gues. No major effect on T-cell/keratinocyte adherence was observed wh en PTX was present during the pre-incubation of keratinocyte monolayer s with tumor necrosis factor-alpha or interferon-gamma prior to the ad hesion assay. In keratinocyte monolayers the interferon-gamma or tumor necrosis factor-alpha induced intercellular adhesion molecule-1 expre ssion could not be inhibited by PTX. However, when PTX was added to sh ort-term organ cultures of normal human skin biopsies, the lipopolysac charide- and tumor necrosis factor-alpha-induced keratinocyte intercel lular adhesion molecule-1 expression was blocked completely. The inter feron-gamma-induced ICAM-1 expression was not blocked by PTX. The resu lts presented herein suggest that impaired T-cell/keratinocyte binding may be one of the mechanisms by which PTX exerts a beneficial effect in certain inflammatory dermatoses.